Pharmaceutical dosage forms can be in the form of single-unit dosage forms such as tablets, or multi-particulate dosage forms such as pellets. Pellets can be flowable, substantially spherical particulates or rods, for example. Pellets can have a uniform composition or can be in the form of a coated particle such as an inert core having a coating comprising an active pharmaceutical ingredient (API) and optionally excipients. Coating of the cores with the API can be followed by coating of the particles with an extended-release polymer. Optionally, the API-coated particles can be incorporated into an extended release matrix composition. Advantages of dosage forms based on pellets include variable dosage strength without formulation changes, ease of combining incompatible agents, and application of extended-release technology.
There are several manufacturing techniques that can be employed in the formation of pellet dosage forms. Extended-release oral dosage forms of APIs may be prepared using a Wurster process to coat a solution of the API onto inert spheroid particles. This process is characterized by the location of a spray nozzle at the bottom of a fluidized bed of solid particles. The particles are suspended in a fluidizing air stream that is designed to induce a cyclic flow of the particles past the spray nozzle. The nozzle sprays an atomized flow of coating solution, suspension, or other coating vehicle. The Wurster process, while effective, can be time-consuming and can add to manufacturing costs.
A less time-consuming method used to coat APIs is a rotor-granulator process in which centrifugal force, fluidization air velocity, and gravitational force all contribute to the efficiency of the process. In one typical rotor-granulator process, an API powder is deposited on an inert core in the presence of a binder solution. In another typical rotor granulation process, a suspension of the API in a suspending agent is employed. The suspended or powder particles of the API can act to control the size of the atomized droplets. The suspended or powder API particles thus effectively act as a dusting powder to reduce agglomeration that can compete with API layering. In the absence of API particles, e.g., in the presence of an API either wholly soluble or soluble to an appreciable extent in the binder solution, rotor-granulation is usually not performed due to stickiness, slow application rates, and/or formation of a rough surface texture on the particles.
In view of the foregoing problems, the remains a need for improved multi-particulate dosage forms and methods of making the dosage forms.